Efficacy of Ramelteon on Transient Insomnia in Healthy Adults

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00671398
Recruitment Status : Completed
First Posted : May 5, 2008
Last Update Posted : February 28, 2012
Information provided by (Responsible Party):

May 1, 2008
May 5, 2008
February 28, 2012
December 2002
May 2003   (Final data collection date for primary outcome measure)
Latency to Persistent Sleep from 1 night of polysomnography (PSG) recording in a sleep laboratory. [ Time Frame: Day 1 ]
Latency to persistent sleep as determined by one night PSG evaluation in a sleep lab. [ Time Frame: Single dose, one day. ]
Complete list of historical versions of study NCT00671398 on Archive Site
  • Total Sleep Time. [ Time Frame: Days 1 and 2. ]
  • Sleep Efficiency. [ Time Frame: Days 1 and 2. ]
  • Wake Time after Persistent Sleep Onset. [ Time Frame: Days 1 and 2. ]
  • Number of Awakenings after Persistent Sleep. [ Time Frame: Days 1 and 2. ]
  • Subjective Sleep Latency. [ Time Frame: Day 2 ]
  • Subjective Total Sleep Time. [ Time Frame: Day 2 ]
  • Subjective Sleep Quality. [ Time Frame: Day 2 ]
  • Subjective Wake Time after Sleep Onset. [ Time Frame: Day 2 ]
  • Subjective Number of Awakenings. [ Time Frame: Day 2 ]
  • Subjective Ease of Falling Back to Sleep after Awakening. [ Time Frame: Day 2 ]
  • Stage 1 Nonrapid Eye Movement (NREM) Sleep [ Time Frame: Day 2. ]
  • Stage 2 Nonrapid Eye Movement (NREM) Sleep [ Time Frame: Day 2. ]
  • Stage 3/4 Nonrapid Eye Movement (NREM) Sleep [ Time Frame: Day 2. ]
  • Latency to Rapid Eye Movement (REM) Sleep [ Time Frame: Day 2. ]
  • Percentage of Total Sleep Time in REM Sleep [ Time Frame: Day 2. ]
  • Objective and subjective measures of efficacy. [ Time Frame: Single dose, one day ]
  • Sleep architecture variables. [ Time Frame: Single dose, one day ]
  • Residual pharmacological effects. [ Time Frame: Single dose, one day ]
  • Safety variables including adverse events, laboratory tests, vital signs, ECG results, and physical examination findings. [ Time Frame: Single dose, one day ]
Not Provided
Not Provided
Efficacy of Ramelteon on Transient Insomnia in Healthy Adults
A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter, Single-Dose Study of TAK-375 in Healthy Adult Volunteers in a Sleep Lab Model of Transient Insomnia
The purpose of this study is to evaluate the safety and efficacy of Ramelteon, once daily (QD), in healthy subjects within a sleep lab.

Insomnia is characterized by difficulties initiating and maintaining sleep, or of non-restorative and non-refreshing sleep. Transient insomnia affects approximately one-third to one-half of the US population, based on the results of 2 surveys of representative samples of the adult US population conducted by the Gallup Organization in which respondents were asked if they had "ever had difficulty sleeping." Based on reports of "regular" or "frequent" sleep difficulty, results from the same studies suggest that approximately one-tenth of the US population experiences chronic insomnia. The ideal treatment for insomnia would reduce the latency to onset of sleep and increase total sleep time, without a negative impact on sleep architecture and without safety concerns or next-day effects.

Ramelteon is a selective melatonin-1 receptor agonist under global development by Takeda Chemical Industries, Ltd., for the treatment of transient and chronic insomnia and for the treatment of Circadian Rhythm Sleep Disorders.

This study is being conducted to evaluate the safety and efficacy of a single dose of Ramelteon in normal healthy subjects in a sleep lab model of transient insomnia. Participation is this study is anticipated to be about 3 weeks.

Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Transient Insomnia
  • Drug: Ramelteon
    Ramelteon 8 mg, tablets, orally for one night only.
    Other Names:
    • Rozerem™
    • TAK-375
  • Drug: Ramelteon
    Ramelteon 16 mg, tablets, orally for one night only
    Other Names:
    • Rozerem™
    • TAK-375
  • Drug: Placebo
    Ramelteon placebo-matching tablets, orally for one night only
  • Experimental: Ramelteon 8 mg QD
    Intervention: Drug: Ramelteon
  • Experimental: Ramelteon 16 mg QD
    Intervention: Drug: Ramelteon
  • Placebo Comparator: Placebo
    Intervention: Drug: Placebo
Zammit G, Schwartz H, Roth T, Wang-Weigand S, Sainati S, Zhang J. The effects of ramelteon in a first-night model of transient insomnia. Sleep Med. 2009 Jan;10(1):55-9. doi: 10.1016/j.sleep.2008.04.010. Epub 2008 Aug 8.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
May 2003
May 2003   (Final data collection date for primary outcome measure)

Inclusion Criteria

  • Females of childbearing potential who are sexually active must agree to use adequate contraception, and can neither be pregnant nor lactating from Screening throughout the duration of the study.
  • Habitual bedtime is between 8:30 p.m. and 12:00 a.m.
  • Sleeps 6.5 to 8 hours per night and has a subjective sleep latency of less than or equal to 30 minutes.
  • Body mass index between 18 and 34, inclusive.

Exclusion Criteria:

  • Any history of insomnia.
  • Spent one or more nights in a sleep laboratory.
  • Epworth Sleepiness Scale score of greater than 10.
  • Known hypersensitivity to Ramelteon or related compounds, including melatonin.
  • Previously participated in a study involving Ramelteon.
  • Participated in any other investigational study and/or taken any investigational drug within 30 days or five half-lives prior to Day 1, whichever is longer.
  • Sleep schedule changes required by employment (ie, shift work) within three months preceding Day 1 or has flown across greater than three time zones within seven days prior to screening.
  • Participated in a weight loss program or substantially altered their exercise routine within 30 days prior to Day 1.
  • History of seizures, sleep apnea, chronic obstructive pulmonary disease, restless leg syndrome, schizophrenia, bipolar disorder, mental retardation, or cognitive disorder.
  • History of a psychiatric disorder (including anxiety or depression) within the past 12 months.
  • History of drug addiction or drug abuse within the past 12 months.
  • Any physical or psychiatric disorder that may be associated with sleep disturbance.
  • History of alcohol abuse within the past 12 months, as defined in Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised and/or regularly consumes 4 or more alcoholic drinks per day.
  • Current significant neurological, hepatic, renal, endocrine, cardiovascular, gastrointestinal, pulmonary, hematologic or metabolic disease.
  • Uses tobacco products during nightly awakenings.
  • Any clinically important abnormal finding as determined by a medical history, physical examination, electrocardiogram, or clinical laboratory tests, as determined by the investigator.
  • Positive hepatitis panel.
  • Positive urine drug screen including alcohol at screening or a positive breathalyzer test at check-in.
  • Any additional condition(s) that in the investigator's opinion would

    • affect sleep-wake function
    • prohibit the subject from completing the study
    • not be in the best interest of the subject.
  • Is required to take or continues taking any disallowed medication, prescription medication, herbal treatment or over-the counter medication, including:

    • Anxiolytics
    • Hypnotics
    • Antidepressants
    • Anticonvulsants
    • Sedating H1 antihistamines
    • Systemic steroids
    • Respiratory stimulants (eg, theophylline)
    • Decongestants
    • Over-the-counter and prescription stimulants
    • Over-the-counter and prescription diet aids
    • Central nervous system active drugs
    • Narcotic analgesics
    • All beta blockers
    • St. John's Wort
    • Kava-kava
    • gingko biloba
Sexes Eligible for Study: All
18 Years to 64 Years   (Adult)
Contact information is only displayed when the study is recruiting subjects
United States
U1111-1114-8626 ( Registry Identifier: WHO )
Not Provided
Not Provided
Not Provided
Study Director: VP Clinical Science Takeda
February 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP